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Integrin alpha(iib)beta(3) and its antagonism

Academic Article
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Overview

authors

  • Quinn, M. J.
  • Byzova, T. V.
  • Qin, J.
  • Topol, Eric
  • Plow, E. F.

publication date

  • June 2003

journal

  • Arteriosclerosis, Thrombosis, and Vascular Biology  Journal

abstract

  • AlphaIIbbeta3, the major membrane protein on the surface of platelets, is a member of the integrin family of heterodimeric adhesion receptors. The alphaIIb and beta3 subunits are each composed of a short cytoplasmic tail, a single transmembrane domain, and a large, extracellular region that consists of a series of linked domains. Recent structural analyses have provided insights into the organization of this and other integrins and how a signal is initiated at its cytoplasmic tail to transform the extracellular domain of alphaIIbbeta3 into a functional receptor for fibrinogen or von Willebrand factor to support platelet aggregation and thrombus formation. These functions of alphaIIbbeta3 have been targeted for antithrombotic therapy, and intravenous alphaIIbbeta3 antagonists have been remarkably effective in the setting of percutaneous coronary interventions, showing both short-term and long-term mortality benefits. However, the development of oral antagonists has been abandoned on the basis of excess of mortality in clinical trials, and the extension of therapy with existing alphaIIbbeta3 antagonists to broadly treat acute coronary syndromes has not fully met expectations. An in-depth understanding of how antagonists engage and influence the function of alphaIIbbeta3 and platelets in the context of the new structural insights may explain its salutary and potential deleterious effects.

subject areas

  • Angioplasty, Balloon, Coronary
  • Antibodies, Monoclonal
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Coronary Disease
  • Drug Design
  • Humans
  • Models, Molecular
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Protein Conformation
  • Structure-Activity Relationship
  • Thrombosis
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Research

keywords

  • acute coronary syndromes
  • aggregation
  • platelet function inhibitors
  • platelets
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Identity

International Standard Serial Number (ISSN)

  • 1079-5642

Digital Object Identifier (DOI)

  • 10.1161/01.atv.0000066686.46338.f1

PubMed ID

  • 12637342
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Additional Document Info

start page

  • 945

end page

  • 952

volume

  • 23

issue

  • 6

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